This invention relates to the preparation of plasminogen activators useful as therapeutic and diagnostic agents.
It has been recognized that plasminogen activators are useful in the treatment of blood clots. By introduction of such an activator to a human blood stream in sufficient quantities and duration, a blood clot that has occurred can be dissolved.
The procedures used in the past for isolating plasminogen activators have been characterized by their complexity and costliness. In the case, for instance, of urokinase, the plasminogen activator found in urine, the yield of the known commercial process is so low that a great quantity of urine must be collected and processed in order to treat a single patient. Isolation of urokinase from other sources, as from kidney tissue culture medium, or isolation of other plasminogen activators, such as streptokinase, likewise involves many steps, which are either costly, or may be associated with adverse immunological reactions. Moreover, the commercially available activators for clinical use (Abbokinase and Streptokinase) are known to have a low affinity for fibrin clots and therefore may not be optimally effective or may be associated with adverse side effects due to generalized proteolysis.
References regarding prior isolation of urokinase are the following:
(a) White, W. F.; Barlow, G. H.; Mozen, M.M.; The Isolation and Characterization of Plasminogen Activators [Urokinase] from Human Urine. Biochemistry, Vol. 5, pp. 2,160-2,169, 1966;
(b) Pye, E. K.; Maciag, T.; Kelly, P.; Iyznger, M. R.; Purification of Urokinase by Affinity Chromotography In: Thrombosis and Urokinase, Eds. R. Paoletti and S. Sherry. Academic Press, London, New York, San Francisco 1977.